Previous findings of widespread transcriptomic alteration in tissues from connexin null mice
raise the issue of whether the transcriptomic changes are directly due to connexin down-
regulation or to “compensatory” developmental alterations for the missing gene. To start
addressing this question, the authors compared with wild-type control the gene expression
profiles of connexin43 (Cx43) knockout and Cx43siRNA knockdown wild-type cortical astro-
cytes. Array analysis revealed remarkable parallelism of transcriptomic changes in knockout
and knockdown astrocytes, with similarly altered genes being located on all chromosomes and
encoding proteins involved in a wide diversity of cell functions. Moreover, gene expression
variability was analogously higher in Cx43 null and siRNA-treated astrocytes, and expression
interlinkages were similarly altered among a selected subset of genes. This highly significant
overlap between transcriptomic alterations in Cx43 knockout and knockdown astrocytes sug-
gests that the widespread changes more likely reflect connexin-dependent Gene Regulatory
Networks rather than developmental compensation for the missing gene.